What is the clinical evidence from this study?

Study design: Observational. Population: Healthy participants (n=513). Intervention: Genetic variants (CYP2C19, 3p25, 17q11). Primary outcome: Circulating clopidogrel active metabolite levels (p=9.5×10).

What question did this study set out to answer?

Identify novel genetic variants that regulate circulating clopidogrel active metabolite levels and explain interindividual variation in antiplatelet drug response.

February 15, 2017Pharmacogenetics and GenomicsOpen Access

Genome-wide analysis of clopidogrel active metabolite levels identifies novel variants that influence antiplatelet response

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Key result

The CYP2C19 locus (P=9.5×10) and novel variants on chromosomes 3p25 and 17q11 were identified as significant genetic determinants of circulating clopidogrel active metabolite levels.

Why the study?

What genetic variants are associated with circulating clopidogrel active metabolite levels in healthy participants?

Population

513 healthy participants

Design

Cross-sectional

Authors

JBJoshua BackmanRegeneron (United States)JOJeffrey R. O’ConnellUniversity of Maryland, Baltimore KTKeith TannerUniversity of Maryland, Baltimore

Discussion

Member takes

Implication

Novel loci extend CYP2C19 pharmacogenetics of clopidogrel; leaves open validation and outcome impact in patients.

Key Points

Identify novel genetic variants that regulate circulating clopidogrel active metabolite levels and explain interindividual variation in antiplatelet drug response.
Conducted a genome-wide association study of circulating clopidogrel active metabolite concentrations to assess pharmacokinetics in N=513 healthy participants.
Assessed the association between top identified genetic candidate loci and on-clopidogrel ADP-stimulated platelet aggregation.
Confirmed the CYP2C19 locus as the strongest genetic determinant of clopidogrel active metabolite formation (P=9.5×10).
Identified novel genome-wide significant variants at chromosomes 3p25 (rs187941554, P=3.3×10) and 17q11 (rs80343429, P=1.3×10), along with six suggestive loci (P≤1.0×10).
Observed nominal associations with on-clopidogrel ADP-stimulated platelet aggregation across four of the identified loci (P≤0.05).

Study Design

Type

Observational (n=513)

Structured PICO

What genetic variants are associated with circulating clopidogrel active metabolite levels in healthy participants?

Population

513 healthy participants evaluated in a genome-wide association study of circulating clopidogrel active metabolite levels.

Exposure

Clopidogrel administration (implied for measuring active metabolite levels)

Outcome

Circulating clopidogrel active metabolite levelssurrogate

Main Result

p-value: p=9.5×10

A genome-wide association study identifies novel genetic variants beyond CYP2C19 that influence clopidogrel active metabolite levels and platelet aggregation.

Cite This Study

Backman et al. (2017) conducted an observational in Healthy participants (n=513). Genetic variants (CYP2C19, 3p25, 17q11) was evaluated on Circulating clopidogrel active metabolite levels (p=9.5×10). The CYP2C19 locus (P=9.5×10) and novel variants on chromosomes 3p25 and 17q11 were identified as significant genetic determinants of circulating clopidogrel active metabolite levels.

synapsesocial.com/papers/6a92a1b38262cd83d9624273 https://doi.org/10.1097/fpc.0000000000000272

Topics

Dual antiplatelet therapy

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Genome-wide analysis of clopidogrel active metabolite levels identifies novel variants that influence antiplatelet response

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Cite This Study

Topics

Genome-wide analysis of clopidogrel active metabolite levels identifies novel variants that influence antiplatelet response

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Cite This Study

Also Consider

Topics

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